This program aims to demonstrate the applicability and development of new synthetic reactions and principles to problems in organic chemistry related to chemotherapeutically important compounds. The new routes developed will lead to practical approaches to macrolides, steroids, prostanoids, and various other natural products of biological significance. The use of transition metal templates to exercise chemoselectivity, regioselectivity and stereocontrol in an absolute and relative sense constitutes a major aspect of this work. Macrocyclic compounds include macrolide antibiotics (e.g., erythromycin, zealeranone, etc.) and anti-tumor agents (e.g., jatrophone). The metabolites of Vitamin D, the active forms of the vitamin, will involve new methods of cyclization, control of acyclic geometry and control of stereochemistry. A chiral synthesis of steroids (e.g., estrone, testosterone, etc.) uses these templates. An enantioconvergent synthesis of prostanoids will allow access to this important class of natural product in optically pure form. Small ring chemistry and sulfur chemistry will contribute to these efforts. Completion of the total synthesis of the antibiotics pentalenolactone and hirsutic acid will be attempted. Application of these new principles to other classes of biologically important compounds will be considered.